This domain is found in checkpoint proteins which are involved in cell division. This region has been shown to be necessary and sufficient for the binding of Mad3 to Bub3 in Saccharomyces cerevisiae. This domain is present in Bub1 which also binds Bub3 [].
This represents the mitotic checkpoint serine/threonine-protein kinase Bub1. Saccharomyces cerevisiae Bub1 has a paralogue, Mad3, which is also included in this entry. Bub1 forms a complex with Mad1 and Bub3 that is crucial for preventing cell cycle progression into anaphase in the presence of spindle damage [], while Mad3 is a component of the spindle-assembly complex consisting of Mad2, Mad3, Bub3 and Cdc20 []. Mad3 contains a D-box and two KEN- boxes, which function together to mediate Cdc20-Mad3 interaction. Mad3 and an anaphase-promoting complex (APC) substrate, Hsl1, compete for Cdc20 binding in a D-box- and KEN-box-dependent manner [].Similar to its yeast homologues, human Bub1 is a critical component of the mitotic checkpoint that delays the onset of anaphase until all chromosomes have established bipolar attachment to the microtubules. In interphase cells it localises to centrosomes and suppresses centrosome amplification via regulating Plk1 activity []. Mutations in the human Bub1 gene have been linked to cancers [, ].
This family consists of pindle assembly checkpoint protein Mad1. The mitotic spindle checkpoint monitors proper attachment of the bipolar spindle to the kinetochores of aligned sister chromatids and causes a cell cycle arrest in prometaphase when failures occur. Multiple components of the mitotic spindle checkpoint have been identified in Saccharomyces cerevisiae and higher eukaryotes. In Saccharomyces cerevisiae, the existence of a Mad1-dependent complex containing Mad2, Mad3, Bub3 and Cdc20 has been demonstrated [].
Mad2 is a central component of the spindle assembly checkpoint, which is a feedback control that prevents cells with incompletely assembled spindles from leaving mitosis [, ]. In Saccharomyces cerevisiae, it is a component of the mitotic checkpoint complex (MCC) which consists of MAD2, MAD3, BUB3 and CDC20, and of the MAD2-CDC20 subcomplex, both of which appear to be assembled during mitoisis independently of the kinetochore. MCC and presumably the MAD2-CDC20 subcomplex inhibit the ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) by preventing its activation by CDC20 [, , ].
